Cerebral Neoplasms in L-2 Hydroxyglutaric Aciduria: 3 New Cases and Meta-Analysis of Literature Data

SUMMARY: Increasing evidence suggests that patients with L2-HGA have a predisposition to cerebral neoplasms. This may be related to the pathologic accumulation of L2-HG because high amounts of 2-HG have been found in brain neoplasms that have IDH1 mutations. Our experience, on the basis of 11 previously unreported cases of L2-HGA, 3 of which developed cerebral neoplasms during the course of the disease, also supports an association between L2-HGA and cerebral neoplasms. We conducted a meta-analysis of published data, and we identified 295 patients (including our 11 patients) with L2-HGA. In 14 patients, the metabolic disorder was associated with cerebral neoplasms, suggesting an approximately 5% prevalence rate of CNS neoplasms in patients with L2-HGA; nonetheless, it may still be an underestimate. L2-HGA is an important disease “model” that provides further evidence to support the recently proposed pathogenetic role of 2-HG in the development of cerebral neoplasms. 2-HG : 2-hydroxyglutarate IDH : isocitrate dehydrogenase L2-HG : L-2-hydroxyglutarate L2-HGA : L-2-hydroxyglutaric aciduria L2HGDH : L-2-hydroxyglutarate dehydrogenase MDH : malate dehydrogenase PNET : primitive neuroectodermal tumor WHO : World Health Organization